Management of asymptomatic abdominal aortic aneurysm

INTRODUCTION — Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Without repair, ruptured AAA is nearly uniformly fatal. Of the 50 percent of patients with ruptured AAA who reach the hospital for treatment, between 30 and 50 percent will die in the hospital [1,2].

For asymptomatic patients, elective repair of the aneurysm is the most effective management to prevent rupture. However, elective aortic surgery is also associated with risks, and thus, elective AAA repair is not recommended until the risk of rupture exceeds the risks associated with repair. For asymptomatic patients, the risk of AAA rupture generally exceeds the risk associated with elective AAA repair when aneurysm diameter exceeds 5.5 cm [3,4]. Other factors such as the patient's age, rate of aneurysm expansion, and the presence of coexistent peripheral artery disease or peripheral aneurysm are also important to consider when determining when to proceed with elective AAA repair.

For patients with asymptomatic AAA who do not have indications for elective repair, medical treatment is aimed at reducing the risk for future cardiovascular events and limiting the rate of aortic expansion. When elective AAA repair is indicated, the choice between open and endovascular AAA repair is based on anatomic factors, and patient and surgeon preference. Although elective endovascular AAA repair is associated with lower rates of perioperative (30-day) morbidity and mortality compared with elective open repair (<2 versus approximately 5 percent), long-term outcomes are similar [5-7].

The management of the patient with asymptomatic AAA will be reviewed here. The clinical features and issues related to diagnosis and screening, management of symptomatic (nonruptured) and ruptured AAA, and details of surgical and endovascular repair are discussed separately.

●(See "Screening for abdominal aortic aneurysm".)

●(See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm".)

●(See "Clinical features and diagnosis of abdominal aortic aneurysm".)

●(See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm" and "Surgical and endovascular repair of ruptured abdominal aortic aneurysm".)

●(See "Endovascular repair of abdominal aortic aneurysm" and "Open surgical repair of abdominal aortic aneurysm".)

ANEURYSM TERMINOLOGY

Aneurysm definition — An abdominal aorta with a maximal diameter >3.0 cm is considered aneurysmal in most adult patients [3,4,8,9]. Abdominal aortic aneurysm (AAA) most often affects the segment of aorta between the renal and inferior mesenteric arteries (infrarenal) (figure 1); approximately 5 percent involve the renal (pararenal) (image 1) or visceral arteries (suprarenal) [10]. (See "Overview of abdominal aortic aneurysm", section on 'Definitions and aortoiliac anatomy'.)

For the purposes of this discussion:

●Small aneurysms have a diameter <4.0 cm

●Medium aneurysms have a diameter between 4.0 and 5.5 cm

●Large aneurysms have a diameter ≥5.5 cm

●Very large aneurysms have a diameter ≥6.0 cm

Rapid expansion, which is thought to increase the risk for rupture, is defined as an increase in maximal aortic diameter ≥5 mm over a six-month period of time or >10 mm over one year, using the same radiographic method of measurement [4]. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

Clinical presentations — Most AAAs do not produce any symptoms. An occult AAA might be discovered as a result of screening, on routine physical examination, or on imaging studies obtained to evaluate an unrelated condition. Symptomatic AAA refers to any of a number of symptoms (eg, abdominal pain, limb ischemia) that can be attributed to the aneurysm. Symptoms associated with AAA may or may not be due to AAA rupture. The clinical features and diagnosis of AAA and the management of symptomatic (nonruptured) and ruptured AAA are discussed in detail elsewhere. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Clinical presentations' and "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Symptoms'.)

ANEURYSM REPAIR VERSUS CONSERVATIVE MANAGEMENT — Elective abdominal aortic aneurysm (AAA) repair is the most effective management to prevent rupture. However, elective aortic surgery is associated with risks, and thus, elective AAA repair is not recommended until the risk of rupture exceeds the risks associated with repair (anesthetic risk, technique-related risks) [6,7,11]. For asymptomatic patients, randomized trials comparing observation with open or endovascular AAA repair have found that the risk of AAA rupture generally does not exceed the risk associated with elective AAA repair until aneurysm diameter exceeds 5.5 cm (algorithm 1) [12-16]. We agree with guidelines from the Society for Vascular Surgery that recommend observation for asymptomatic AAA <5.5 cm in diameter based upon these trials [7,17]. (See 'Aneurysm diameter and rupture risk' below.)

The timing of AAA repair may be affected by other factors such as the presence of coexistent peripheral artery disease or peripheral aneurysm (eg, iliac aneurysm, femoral aneurysm) and other factors that increase the risk of rupture, including advanced age and rapid aneurysm expansion. (See 'Other considerations' below.)

Although repair may not be warranted in patients with AAA diameter <5.5 cm, these patients remain at risk for aneurysm expansion. As such, management consists of ongoing clinical evaluation and AAA surveillance, and risk modification. (See 'Conservative management' below.)

Aneurysm diameter and rupture risk — Rupture is the most feared complication and is associated with high morbidity and mortality. Aneurysm diameter is the strongest predictor of aneurysm rupture, with risk increasing markedly at aneurysm diameters greater than 5.5 cm (figure 2) [12,18-25]. Larger aneurysm diameter and faster rate of aneurysm expansion correlate to an increased likelihood of symptoms and complications. While it is uncommon for AAAs smaller than 5 cm to rupture, it does happen [26,27]. As an example, in one systematic review that included 21 studies of patients with AAA also reporting AAA outcomes, 37 of 2323 (1.6 percent) with AAA between 3.0 and 5.4 cm went on to rupture [28]. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

Randomized trials — Based upon observational studies of the natural history of AAA showing that it was uncommon for asymptomatic AAA smaller than 5 cm to rupture, this was the traditional threshold above which open aneurysm repair was performed [27,29]. Whether this represented optimal management was addressed in randomized trials comparing aneurysm repair with nonoperative management plus surveillance imaging for medium-sized aneurysms (4.0 to 5.5 cm), with two trials using open AAA repair [12,13], and three later trials using endovascular aneurysm repair [14-16,30,31]. These trials and a subsequent meta-analysis found no advantage to early repair (open or endovascular) for AAA measuring 4.0 to 5.5 cm [32].

Observation versus open repair — In the United Kingdom (UK) Small Aneurysm and (US) Aneurysm Detection and Management (ADAM) trials, which were predominantly composed of men, the risk of death due to rupture during the period of surveillance of medium-sized (4.0 to 4.4 cm) AAA was lower than the risk of death from open AAA repair [12,13,33]. A later analysis pooled results from both trials and reported no differences in survival between immediate open repair and surveillance (2.6- to 8-year follow-up) for any diameter in the range of 4 to 5.5 cm, for males or females, or for any age [34].

The important points of these trials are summarized:

●UK Small Aneurysm trial – The UK Small Aneurysm trial randomly assigned 1090 patients (83 percent men) with asymptomatic AAA with a diameter of 4.0 to 5.5 cm to elective surgery or observation with ultrasound surveillance every six months [12,33,35,36]. Open surgical repair was performed if the aneurysm diameter exceeded 5.5 cm, expanded more than 10 mm in a year, or became tender or symptomatic. The two groups had similar cardiovascular risk factors at baseline. After a mean follow-up of eight years, the following findings were noted:

•An initial survival advantage was apparent for patients in the observation group because of a 30-day operative mortality of 5.4 percent. However, at eight-year follow-up, mortality was significantly lower for patients who underwent elective surgery (43 versus 48 percent). Equipoise between the therapies was achieved at approximately five years (figure 3) (the point at which the area under the survival curve is equal).

•The mean duration of survival was the same in the two groups (6.7 versus 6.5 years) since early mortality was offset by improved late survival in the group that underwent surgery. The authors ascribe the improved late survival in the surgery group to beneficial changes in lifestyle, particularly smoking cessation, which was more frequent in this group.

•During follow-up of the surveillance group, the median aneurysm growth rate was 3.3 mm per year and the mean risk of aneurysm rupture was 1.6 percent per year during the initial follow-up period but increased to 3.2 percent per year during the last three years of follow-up, as expected, since the aneurysms under surveillance were larger during this later time period.

•The risk of AAA rupture was four times higher in females compared with males (hazard ratio [HR] 4.0, 95% CI 2.0-7.9). The incidence of fatal rupture was also significantly greater for females compared with males (19 versus 14 percent). (See 'Female sex' below.)

●ADAM trial – The Aneurysm Detection and Management (ADAM) Trial randomly assigned 1136 patients (over 99 percent male) aged 50 to 79 years with AAA diameter between 4.0 to 5.4 cm to open aneurysm repair or surveillance [13]. Elective surgery was performed when the aneurysm expanded to >5.5 cm or became symptomatic. Operative mortality in this trial was 2.7 percent. After 4.9 years of follow-up, there were no differences in mortality (25 versus 21.5 percent) or aneurysm-related death (3 versus 2.6 percent) between the surgery and surveillance groups. In the surveillance arm, 62 percent of the patients eventually required surgery. AAA rupture occurred in 1.9 percent (0.6 percent per year).

Observation versus endovascular repair — The UK Small Aneurysm Trial and the ADAM trial were performed prior to the widespread use of endovascular aneurysm repair (EVAR). Trials comparing EVAR to observation for AAA <5.5 cm similarly have found no significant mortality benefit for AAA repair (EVAR) and nonoperative management, and these studies lend further support to the 5.5 cm threshold established from earlier randomized trials [14-16,30,31,37-39]. Despite the lower perioperative mortality rate associated with EVAR, there appears to be no advantage to elective EVAR repair for small and medium-sized aneurysms.

Large observational studies — In large observational studies of individuals identified as having small or medium sized AAA as a result of participation in screening studies and followed with surveillance ultrasound, the overall risk of AAA rupture was low [40]. In a review of males older than 65 in the National Health Service AAA Screening Programme in the United Kingdom, 1846/18,652 (10 percent) of the males met criteria for referral for AAA repair during the surveillance period because AAA diameter exceeded 5.5 cm or for other reasons (eg, associated iliac aneurysm, tenderness, rapid expansion) [40]. The overall rate of rupture was very low at 0.17 percent (31 of 18,652); however, most males (29/31) who presented with ruptured small or medium diameter aneurysms died.

Other considerations — A decision for elective repair of asymptomatic AAA relies primarily on determining rupture risk based upon aneurysm diameter >5.5 cm. However, the diameter threshold for repair is not absolute. Deciding when to perform elective AAA repair should also account for the natural history of AAA and factors that increase the risk for aneurysm expansion or rupture such as female sex, advanced age, expansion rates, and aneurysm morphology. Timing of AAA repair may also be affected by coexistent vascular disease or other peripheral artery aneurysms. These issues are reviewed below. Additional information regarding risk factors associated with AAA expansion and rupture can be found in the linked topic. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

Some studies have also identified disparities in rupture rates based upon insurance status [41,42]. Differences are multifactorial but can be explained in part by lower surveillance rates for patients with known AAA for patients eligible for Medicaid insurance. This finding highlights the need for and value of surveillance for all patients with AAA that does not meet criteria for operative repair, preferably using a standardized protocol. (See 'Follow-up and surveillance' below.)

Female sex — Differences in demographics, natural history, and outcomes have raised interest in better defining the value that determines the presence of AAA in females and, furthermore, the ideal threshold for repair. Randomized trials that have determined these values, as discussed above, are comprised predominately of male subjects. (See 'Randomized trials' above.)

For females, a lower threshold of 5 cm may be justified for elective repair of asymptomatic AAA due to the higher rate of rupture in females compared with males for AAA of the same diameter [12,17,43,44]. Using a smaller diameter of aorta as the threshold for diagnosis would alter the commonly cited prevalence of AAA for females [45] and might improve the likelihood of females being offered repair. Moreover, the proportion of females who meet all eligibility criteria for endovascular repair related to anatomy may decrease as aortic diameter increases [46-48]. However, the impact of this on overall survival is less certain. Perioperative mortality with AAA repair is higher using current indications for repair, and as a result, females may be more likely to die from early intervention than from rupture during ongoing surveillance [49-54]. On the other hand, mortality following repair of AAA at a lower threshold diameter is unknown. It may be similar or worse, or possibly improved if such patients are more medically fit with more favorable anatomy at the time of repair.

Based on the studies below and others, a reasonable compromise may be to offer AAA repair at the lower threshold of 5.0 cm to females who are at low operative risk, while using the typical threshold for females who have a higher operative risk [49,55-59].

●In a systematic review comparing AAA in females with males, a higher proportion of females were not offered intervention (34 versus 19 percent; odds ratio [OR] 2.3, 95% CI 1.2-4.2, four studies), a smaller proportion of females were considered eligible for endovascular repair (34 versus 54 percent; OR 0.44, 95% CI 0.32-0.62, five studies), and, when repair was performed, operative mortality was higher for females regardless of the method of repair (EVAR: 2.3 versus 1.4 percent; OR 1.7, 95% CI 1.4-2.0; open repair: 5.4 versus 2.8 percent, OR 1.8, 95% CI 1.4-2.3, nine studies) [55].

●In a review of 4045 patients from the Vascular Study Group of New England (VSGNE) database that included 890 females, aneurysm diameter alone was most predictive of rupture for men, whereas for females, aortic size index (ASI = aneurysm diameter [cm]/body surface area [m²]) was predictive (ASI >3.5-3.9: OR 6.4, 95% CI 1.7-24.1; ASI ≥4.0: OR 9.5, 95% CI 2.3-39.4) [56]. However, the risk of death from elective repair was also increased for females, in part related to a later age at presentation.

●A follow-up study compared survival differences between those with AAA 4.0 to 5.4 cm undergoing immediate open repair versus surveillance among participants of the UK Small Aneurysm Trial and the ADAM trials (n = 2226) [53]. Survival was similar for both females and males independent of treatment (open repair or surveillance). Survival for females was also similar for moderate-size AAA (5.0 to 5.4 cm) versus smaller (<4.0 to 5 cm) aneurysms. Using a risk-adjusted model, the risk-adjusted survival probability following repair was higher when the aneurysm reached or exceeded 5 cm.

Patient age — Younger patients with AAA with a long life expectancy will likely require repair at some point in their lives [12]. The likelihood of receiving surgery at some point in the future for medium-sized aneurysms (4.0 to 5.5 cm), is 50 percent at three years, 60 to 65 percent at five years, and 70 to 75 percent at eight years (figure 4) [12,13,33,36,60].

Among older patients, endovascular repair is associated with an early survival advantage that gradually decreases over time. Overall five-year survival following AAA repair was 69 percent in one systematic review, with age correlating with worse survival [61]. A propensity-score-matched cohort study involving 39,966 matched pairs of United States Medicare beneficiaries (>65 years of age) found no significant long-term survival advantage for endovascular repair even though perioperative (30-day) mortality was significantly lower for endovascular compared with open repair (1.6 versus 5.2 percent) [62]. The survival advantage for EVAR lasted only through the first three years of follow-up.

Although small case series have documented acceptable outcomes for EVAR in carefully selected octogenarians and nonagenarians [63-67], continued observation may be warranted for AAA that exceeds 5.5 cm in older patients, particularly among those who are frail for whom a long-term benefit is unlikely [68]. Those with medical comorbidities often die from associated illnesses. (See 'Counseling the high-risk patient' below.)

Rapid expansion — Earlier repair may benefit patients with well-documented rapid aneurysm expansion (>5 mm in six months or 10 mm per year) on serial imaging studies performed by the same modality [12]. Some data suggest that rapidly expanding AAAs are more likely to have symptoms and have a higher risk of rupture. Rapid expansion may represent instability of the aortic wall and may be a sign of impending aortic rupture. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Risk factors'.)

Aneurysm morphology — Saccular AAA may be more likely to become symptomatic compared with a fusiform AAA of the same size, but there is no clear evidence that saccular AAA represents a special hazard mandating repair regardless of size [7]. When saccular aneurysm is identified, care should also be taken to rule out infectious etiology or other special circumstances that may require special attention [69]. (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm", section on 'Symptomatic (non-ruptured) AAA'.)

Coexistent aneurysm or peripheral artery disease — Repair of AAA with a diameter that has not exceeded the threshold of 5.5 cm may be reasonable in patients with other associated arterial diseases such as aneurysmal disease of the iliac, femoral, or popliteal arteries, or symptomatic coexistent aortoiliac occlusive arterial disease. It is important to note that aneurysm expansion tends to be less rapid in patients with peripheral artery disease or diabetes mellitus [13,70]. (See "Popliteal artery aneurysm" and "Iliac artery aneurysm".)

Repair of suprarenal and/or thoracoabdominal aneurysms involves more extensive surgery and greater operative risk. For this reason, and considering that the normal diameter of the proximal aorta is larger, repair of such aneurysms is typically not undertaken until the aortic diameter has exceeded 5.5 to 6.0 cm. (See "Management of thoracic aortic aneurysm in adults".)

MEDICAL RISK ASSESSMENT — The primary goal of elective AAA repair is to prevent rupture and minimize aneurysm-related morbidity and mortality. The assessment of risk for elective aneurysm repair versus the risks of observation should include the patient's expected survival from other medical conditions. Repair may not be warranted if the expected mortality rate from another condition is higher than the expected aneurysm-related mortality. Updated guidelines from the Society for Vascular Surgery (SVS) for the care of patients with AAA suggest the use of the Vascular Quality Initiative perioperative mortality risk score to aid decision making for elective AAA [7]. (See "Open surgical repair of abdominal aortic aneurysm", section on 'Estimation of perioperative risk'.)

Patients with coexistent coronary artery disease and cigarette smokers with chronic obstructive pulmonary disease are more likely to experience serious perioperative complications (eg, myocardial ischemia, arrhythmias, pneumonia) [71,72].

●Patients diagnosed with AAA have an increased risk for cardiovascular disease, and all patients with AAA should undergo cardiovascular risk assessment [28,73-75]. This increase in risk was illustrated in a prospective study that identified AAA in 8.8 percent of patients screened; AAA was <3.5 cm in diameter in 88 percent of the patients [73]. During a 4.5-year follow-up period, patients with AAA had a higher overall mortality than those without AAA (adjusted risk [RR] 1.3, 95% CI 1.04-1.67) and an increased risk of incidental cardiovascular disease (adjusted risk 1.57, 95% CI 1.18-2.07). In a systematic review that included 21 studies of patients with small AAA (<5.5 cm) also reporting cardiovascular outcomes (although there was wide variability in definitions used), the prevalence of ischemic heart disease among those with small AAA was 45 percent, 27 percent for myocardial infarction, and 14 percent for stroke [28]. (See "Evaluation of cardiac risk prior to noncardiac surgery" and "Management of cardiac risk for noncardiac surgery".)

●The prevalence of smoking in randomized trials among patients undergoing AAA repair is 24 to 40 percent [12,76-79]. Current smokers and patients with a significant smoking history or pulmonary disease should be evaluated based upon standard guidelines for assessing perioperative risk. Patients with severe pulmonary disease who are not candidates for general anesthesia may be considered for endovascular aneurysm repair if there are no other contraindications for endovascular repair. Smoking cessation prior to elective surgery is discussed in detail elsewhere. (See "Evaluation of perioperative pulmonary risk" and "Strategies to reduce postoperative pulmonary complications in adults", section on 'Smoking cessation'.)

The risk for perioperative morbidity and mortality related to elective AAA repair is also increased in those with renal dysfunction, female patients, and older patients.

Renal failure is overall uncommon after AAA repair. One study identified six risk factors associated with renal failure (defined as a requirement of postoperative renal replacement therapy) following open AAA repair [80]. These included preoperative creatinine >1.7 mg/dL, age >75 years, symptomatic AAA, AAA rupture, treated hypertension, and pulmonary disease. Preoperative renal dysfunction was the strongest predictor of postoperative renal failure. In a study that evaluated data from the UK EVAR trials, there did not appear to be any significant long-term difference in renal function comparing endovascular with open AAA repair [81].

CONSERVATIVE MANAGEMENT — Based upon the result of randomized trials, patients with AAA <5.5 cm in diameter should be managed conservatively. The natural history of AAA is generally one of progressive expansion [82]. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

Follow-up and surveillance — Patients with small and medium-sized AAA and high-risk patients who are being managed conservatively should undergo periodic clinical evaluation to evaluate for any symptoms that might be related to the aneurysm, and to monitor blood pressure and the success of risk reduction strategies. (See 'Cardiovascular risk reduction' below.)

Only a small proportion of patients diagnosed with AAA as part of a screening program meet the criteria for AAA repair at the time of the initial diagnosis or later during surveillance. Based on information from screening studies, patients with AAA <5.5 cm can be reassured that the risk of rupture is very small, although not zero, underscoring the need for period clinical evaluation and surveillance of aneurysm diameter [40]. Indeed, patients with small aneurysms who do not undergo scheduled surveillance or who are lost to follow-up may be up to six times more likely to present with rupture [83]. Among patients identified with small AAA (≥3.6 cm), in one study, follow-up was overall poor at 65 percent [84]. The rate of follow-up is even poorer for those identified incidentally on imaging studies performed for another reason [85]. During a period of follow-up, about 10 percent of patients under surveillance whose AAA was identified as a result of a screening examination may be expected to require surgery related to aneurysmal expansion (nonruptured) during their lifetime. It is important to note that only a small fraction of all clinically recognized AAA, small or large, are identified as the result of screening programs. Overall, for all methods of AAA diagnosis (ie, screening, physical examination, incidental imaging), the likelihood of needing surgical repair due to initial aneurysm diameter or enlargement during a period of surveillance is approximately 70 percent.

For patients who elect no repair or who are not candidates for any type of repair, ongoing evaluation and surveillance is not needed. (See 'Counseling the high-risk patient' below.)

Imaging

Aneurysm imaging — Patients with asymptomatic AAA under observation for possible future repair should undergo periodic imaging to assess for aortic expansion, but evidence to support an optimal surveillance schedule is not clear [12,13,17,36,86-88]. We generally obtain annual ultrasound for aneurysms <5.5 cm; however, a more frequent interval (eg, every six months) may be used depending upon the characteristics of the aneurysm (eg, larger diameter ≥4.5, greater expansion rate) or patient-related factors (eg, patient anxiety).

Our preference for annual ultrasound for AAA <4.5 cm (or more frequently for larger aneurysm, or other factors) is based on the low cost of ultrasound and the following reasons:

●Annual clinical examination and risk reduction assessment can be performed concurrently with ultrasound surveillance [89,90].

●When the aneurysm surveillance interval is extended beyond one year, the inherent inaccuracies associated with aortic measurements using ultrasound and computed tomography (CT) become more relevant. Multiple studies obtained over more frequent intervals help resolve conflicts and are more likely to capture rapid aortic expansion.

●There is a potential for patients to be lost to follow-up when extended surveillance intervals are used. Gaps in surveillance of AAA are associated with AAA rupture [83,84]. Thus, when a longer surveillance interval is chosen, it is important to have a reminder system in place. In a database review of nearly 10,000 patients with known AAA who underwent repair of an intact or ruptured aneurysm, gaps in surveillance were defined as no imaging within one year prior to surgery or no imaging for more than two years after the initial image [83]. Patients with ruptured AAA were significantly more likely to have gaps in surveillance compared with those receiving repair for intact AAA (47.4 versus 11.8 percent). In a multivariate analysis, gaps in surveillance remained the largest predictor of rupture after adjusting for medical comorbidities (odds ratio [OR] 5.82, 95% CI 4.64-7.31).

●Anxiety is often associated with a diagnosis of AAA, and many patients find reassurance with demonstration of aneurysm diameter stability, as well as a fixed surveillance interval [91]. Admittedly, for many patients, these anxieties may be reduced with proper education.

While annual surveillance (or more frequent) is our preference, updated guidelines from the Society for Vascular Surgery (SVS) support longer surveillance intervals for small AAAs and suggest the following surveillance schedule [7,17]:

●For initial ultrasound screening aortic diameter >2.5 cm but < 3.0 cm, rescreening after 10 years

●For AAA 3.0 to 3.9 cm, imaging at 3-year intervals

●For AAA 4.0 to 4.9 cm, imaging at 12-month intervals

●For AAA 5.0 to 5.4 cm, imaging at 6-month intervals

This recommendation was based on studies evaluating aneurysm progression. In the United Kingdom small aneurysm study, surveillance intervals were used to minimize the likelihood of aneurysm expansion to greater than 5.5 cm between screening visits [70]. As might be expected, the recommended intervals for surveillance were shorter for larger aneurysms and longer for smaller aneurysms. Surveillance was every 3 months for AAA 5.0 to 5.4 cm, every 12 months for AAA 4.5 to 4.9 cm, every 24 months for AAA 4.0 to 4.4 cm, and every 36 months for AAA 3.5 to 3.8 cm. In this study, less frequent surveillance was felt to be safe, and the suggested surveillance schedule resulted in a <1 percent chance of an aneurysm surpassing 5.5 cm in diameter between screening visits [92]. These intervals are consistent with those used in the Multicentre Aneurysm Screening Study (MASS) [93]. Based largely upon these studies, multidisciplinary guidelines for the diagnosis and management of peripheral artery disease recommend surveillance every 6 to 12 months using ultrasound or CT for aneurysms 4.0 to 5.4 cm in diameter but a less frequent interval (every two to three years) for aneurysms 3.0 to 4.0 cm in diameter, and every five years for aortic diameter between 2.6 to 2.9 cm [4,7,9,87]. Recommendations for AAA surveillance schedule vary widely around the globe [87].

While most surveillance is based upon aneurysm diameter, there is interest in using AAA sac volume for surveillance [94-96]. AAA sac volume has been noted in research studies to change when AAA diameter has not; however, the significance of this observation is unknown. More frequent CT scanning, which is required for this measurement, is expensive and would subject the patient to additional radiation exposure. Thus, we do not use such measurements for routine AAA surveillance.

Other techniques — Inflammation helps to mediate AAA, and radiographic modalities that can identify inflammation in the aortic wall are being investigated to predict AAA development, growth, and/or rupture [97-102]. Further study is needed to more accurately quantify associations between inflammation within AAA on imaging and subsequent expansion or rupture before these become clinically useful. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Inflammation and the Th2 response'.)

●Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging is one modality that has been investigated for the purpose of tracking aortic mural inflammation but with indeterminant results [98,103]. USPIOs are not sufficiently specific to select out pro- versus anti-inflammatory macrophages. Thus, specific molecular targeting agents for activated (M1) macrophages will likely be necessary to improve the positive/negative predictive value of inflammation imaging for tracking AAA progression/outcomes. In a multicenter cohort study that monitored 342 individuals with AAA ≥4 cm for over two years, USPIO enhancement was identified in 42.7 percent of participants, absent in 55.8 percent, and indeterminant in 1.5 percent [98]. Compared with those without uptake, patients with USPIO enhancement had higher rates for the primary outcome of aneurysm rupture or repair (47.3 versus 35.6 percent). Patients with USPIO enhancement also had increased rates of aneurysm expansion compared with those without uptake (3.1 versus 2.5 mm/year), although this was not independent of current smoking habit. Baseline AAA diameter and current smoking also predicted the primary outcome. However, the addition of USPIO enhancement to the multivariate model did not improve prediction of adverse AAA-related events over clinical features alone. It is also important to note that the additional iron load associated with iron-based contrast agents carries its own risk for long-term cardiovascular disease and cancer risk [104].

●The use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is also promising but inconsistent for predicting AAA expansion or rupture [102,103]. A systematic review revealed that FDG-PET showed that standardized uptake values (SUVs) either had a negative association with AAA growth or nonstatistically significant associations with AAA expansion [102]; other studies have shown a positive association [105].

Safety of antithrombotic therapy

Antiplatelet therapy — While there is no good evidence to support the use of antiplatelet agents for preventing clinical progression of AAA, antiplatelet therapy is indicated as a general intervention to reduce the risk of future cardiovascular events in patients with AAA. (See 'Uncertain benefit for limiting AAA expansion' below and 'Cardiovascular risk reduction' below.)

It is currently unknown whether ASA alone has a substantial effect with respect to hemorrhage in association with AAA rupture. Theoretically, thrombus formation would be impeded; however, the retroperitoneal structures probably play a greater role in limiting the initial expansion of hematoma following AAA rupture. In general, we feel that the beneficial effects of ASA in reducing cardiovascular morbidity and mortality outweigh the theoretic risks of increased bleeding with AAA rupture.

Anticoagulation — Patients with indications for anticoagulation (eg, atrial fibrillation) should be treated as indicated. There is no evidence that chronic anticoagulation alters the natural history of AAA.

Mural thrombus associated with AAA is a consequence of altered flow, but the exact relationship between luminal thrombus volume and pattern of distribution on AAA expansion is not well defined. Mural thrombus associated with AAA is typically firm clot tightly adherent to the aortic wall; however, it can embolize distally, but there are no data to suggest that chronic anticoagulation modifies the risk [106]. If embolization does occur, the patient is considered "symptomatic" and is a candidate for AAA repair. (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm".)

Even in the absence of embolism, the appearance of thrombus that is not adherent to the lateral margins of the aneurysm sac (eg, floating), or changes in mural thrombus (eg, fractured, displaced), may indicate a rapid change has occurred in AAA diameter, or may even herald rupture. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Ruptured versus nonruptured AAA'.)

Thrombolytic therapy — Thrombolytics are commonly used for a variety of indications (eg, acute stroke, pulmonary embolism, acute limb ischemia). There is evidence from case reviews that thrombolytics can destabilize AAA mural thrombus, leading to dislodgement and distal embolism, and possibly to aortic leak [107,108]. When reviewing potential administration of thrombolytic therapies, the overall benefits of treating the underlying condition must be weighed against the possible harms. While bleeding risks predominate, the potential complications related to the aneurysm should be considered, and if it is elected to proceed with thrombolysis, then the patient should also be monitored for possible aneurysm-related complications.

Fluoroquinolone use — Based on data from observational studies that the use of fluoroquinolones may increase the occurrence of aortic aneurysm or dissection [109-113], the US Food and Drug Administration (FDA) issued an updated safety communication in December 2018 stating that fluoroquinolones may increase the occurrence of aortic aneurysm or dissection [114]. Some have suggested that any effect may be more related to inflammatory changes occurring with the infection being treated, rather than a particular antibiotic [115]. Studies published after the FDA communication are reviewed separately. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Fluoroquinolones and other antimicrobials used to treat infection'.)

The FDA recommends the following:

●Avoid prescribing fluoroquinolone antibiotics to patients who have an aortic aneurysm.

●Only prescribe fluoroquinolones to these patients when no other treatment option is available.

●Advise all patients to seek immediate medical treatment for any symptoms associated with aortic aneurysm or dissection. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Symptomatic (nonruptured) AAA' and "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Ruptured AAA' and "Overview of acute aortic dissection and other acute aortic syndromes" and "Clinical features and diagnosis of acute aortic dissection".)

Counseling the high-risk patient — Asymptomatic patients with AAA repair >5.5 cm who have medical comorbidities that increase their risk for repair (open surgical or endovascular) above the expected level may be best managed conservatively, reserving repair only if symptoms develop (including rupture). (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm".)

In a database review by the Vascular Study Group of New England, among 1653 patients undergoing endovascular aneurysm repair, 19 percent were deemed unfit to undergo open aneurysm repair [116]. Patients who were unfit for open repair were older and more likely to have cardiac disease or chronic obstructive pulmonary disease. By contrast, compared with those deemed fit for open AAA repair, patients deemed unfit had significantly higher rates of cardiac (7.8 versus 3.1 percent) and pulmonary (3.6 versus 1.6 percent) complications. Survival for those deemed unfit was significantly worse than those deemed fit (one-year survival 93 versus 96 percent; three-year survival 73 versus 89 percent, and five-year survival 61 versus 80 percent). Even adjusting for age, designation as unfit was a significant predictor of worse five-year survival (hazard ratio 1.6, 95% CI 1.2-2.2). In a review of outcomes in males with screen-detected large AAA deemed not fit for repair, death occurred in 14/34 at a median of 34.9 months after diagnosis, 9 from ruptured AAA [117]. Long-term outcomes for patients deemed unfit for open surgery should also be considered when considering endovascular repair. (See 'Open versus endovascular aneurysm repair' below.)

Expected rupture rates for untreated patients vary depending on the population studied, aneurysm diameter, and other risk factors for rupture (eg, smoking, chronic obstructive pulmonary disease, unmanaged medical conditions). The biology of AAA may also be changing. The risk of rupture and death has been declining, in parallel with reductions in per capita smoking [118]. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

●One study evaluated 198 males with contraindications to repair or refusal [119]. The one-year incidence of rupture (and death) was 9.4 percent for AAA 5.5 to 5.9 cm in diameter, 10.2 percent for AAA 6.0 to 6.9 cm, and 37.5 percent for AAA >7.0 cm.

●In another study of 72 patients who were deemed unfit for AAA repair, median survival for AAA 5.1 to 6.0 cm was 44 months and 11 percent died of rupture; for AAA 6.1 and 7.0 cm, median survival was 26 months and 20 percent died of rupture; and for AAA >7 cm, survival was six months and 43 percent ruptured [120].

●In a later study that included 1514 patients with untreated AAA, cumulative annual rupture rates were 3.5 percent for AAAs 5.5 to 6.0 cm, 4.1 percent for AAAs 6.1 to 7.0 cm, and 6.3 percent for AAAs >7.0 cm [121].

Long-term survival in high-risk patients may be unaffected by repair. The EVAR 2 (Endovascular repair of aortic aneurysm in patients physically ineligible for open repair) trial randomly assigned 404 patients with AAA >5.5 cm and who were aged 60 years or older to endovascular aneurysm repair or no intervention [16]. The endovascular group had a lower risk of aneurysm-related mortality (adjusted hazard ratio [HR] 0.53, 95% CI 0.32-0.89), but there were no significant differences in all-cause mortality (HR 0.99, 95% CI 0.78-1.27) at eight-year follow-up.

Decision making in high-risk patients is difficult but should include a candid discussion with the patient and family or other caretakers. This discussion should include counseling the patient to create an advanced directive detailing the patient's wishes in the event of rupture. Family members or other caretakers should be made aware of these wishes, given that the patient may not be able to report their wishes at the time of aneurysm rupture.

Cardiovascular risk reduction — Multidisciplinary guidelines regard AAA as a coronary heart disease equivalent and recommend risk reduction strategies, which include medical therapy (antiplatelet therapy, statin therapy, antihypertensive therapy), smoking cessation and aerobic exercise to reduce the risk of future cardiovascular events, unless contraindicated [4]. However, these therapies do not appear to significantly reduce rates of AAA expansion [122]. There is also no evidence to suggest that aspirin therapy contributes in any way to initiating AAA expansion or rupture. (See 'Therapies to limit aortic expansion' below and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

In a study that included over 12,000 patients with a diagnosis of AAA, the percentage use of medications to manage cardiovascular risk increased from 2000 to 2012 (from 26 to 77 percent for statins, 56 to 74 percent for antiplatelet agents, and 75 to 84 percent for antihypertensive drugs) [123]. On Kaplan-Meier analysis, five-year survival improved for patients receiving compared with not receiving each therapy (68 versus 42 percent for statins, 64 versus 40 percent for antiplatelet agents, and 62 versus 39 percent for antihypertensive agents).

Managing cardiovascular risk is also important for improving overall outcomes associated with AAA repair (open surgical or endovascular repair) given that approximately one half of patients with small AAA who are being conservatively managed will eventually undergo AAA repair [4,9,124,125]. In a systematic review of 14 cohort studies, statin treatment among nearly 70,000 AAA patients was associated with a 35 percent relative reduction in total mortality (rate ratio 0.65, 95% CI 0.57-0.73) with a median follow-up of 3.1 years [126]. Perioperative (30 day) mortality was not significantly different. Other studies have similarly found a benefit for statin therapy for patients with AAA [122,126-139].

Patients with hypertension should be evaluated and treated to recommended blood pressure goals. No specific antihypertensive therapy has, thus far, been shown to alter the natural history of AAA. Whenever possible, patients should avoid blood pressure spikes. (See "Overview of hypertension in adults" and "Goal blood pressure in adults with hypertension" and 'Uncertain benefit for limiting AAA expansion' below and 'Aerobic exercise' below.)

Therapies to limit aortic expansion — The likelihood that an aneurysm will expand or rupture is influenced by a number of factors, including aneurysm diameter, rate of expansion, sex, ongoing smoking, recent surgery, and other medical factors [86,140]. These risk factors are discussed elsewhere. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Expansion and rupture of AAA'.)

Medical management of AAA is focused on modifiable risk factors for AAA and cardiovascular disease with the goals of reducing the need for intervention due to aneurysm expansion or rupture, reducing morbidity and mortality associated with repair, and reducing cardiovascular morbidity and mortality [141,142]. Among the factors associated with AAA expansion and rupture, smoking is the most important modifiable risk factor, and we recommend smoking cessation for all patients with AAA (see 'Smoking cessation' below). Although reduced aneurysm expansion and rupture risk have not been clearly demonstrated among those who have stopped smoking, smoking cessation has other benefits. In addition, because AAA is regarded as a coronary risk equivalent, we agree with major society guidelines that recommend aspirin (ASA) and statin therapy for patients with AAA to reduce the risk of a future cardiovascular event, unless contraindicated [4,7,9]. Many pharmacologic therapies aimed at limiting AAA expansion and preventing rupture have been investigated, but none has proven successful at achieving these goals, and as such, we suggest not implementing any of the pharmacologic therapies discussed below for the sole purpose of treating AAA. Individual medical conditions should be treated as appropriate (eg, hypertension).

Potentially beneficial therapies

Smoking cessation — Cigarette smoking is the risk factor most strongly associated with aneurysm formation, aneurysm expansion, and aneurysm rupture and is the most important modifiable risk factor in patients with AAA [70,140,142-145]. We agree with multidisciplinary guidelines that individuals diagnosed with AAA and those who have a family history of AAA be advised to stop smoking and offered cessation interventions [4,7,9,146]. Smoking cessation has many other benefits. The management of smoking cessation is discussed in detail elsewhere. (See "Benefits and consequences of smoking cessation" and "Overview of smoking cessation management in adults".)

Smoking cessation is presumed to provide a benefit by reducing the harmful effects of smoking in mediating connective tissue degradation, although this has not been proven [147]. With smoking cessation, the risk of developing AAA slowly declines over time [140,144], but the effect of smoking cessation on AAA that is already formed is unknown. There are no controlled trials of smoking cessation in patients with AAA, and it is unlikely that any such studies will ever be performed. However, former smokers undergoing AAA repair have lower rates of aneurysm-related mortality and all-cause mortality compared with current smokers, suggesting the importance of smoking cessation [148,149]. Smoking cessation for at least two months prior to AAA repair was found in one prospective study to significantly reduce the incidence of postoperative respiratory complications (57 versus 15 percent) [150].

Aerobic exercise — It is widely accepted that higher levels of physical activity are associated with a lower risk of cardiovascular morbidity and death. We agree that patients with AAA should participate in an exercise program for secondary prevention of cardiovascular disease. Patients should be counseled that moderate physical activity such as running, biking, swimming, hiking, or sexual activity and activities such as gardening, golfing, and horseback riding do not precipitate AAA rupture [151]. However, heavy lifting, especially while holding the breath, and other activities that lead to Valsalva transiently induce significant increases in blood pressure and should be avoided.

Moderate physical therapy may also limit aneurysm expansion [152,153]. In experimental aneurysms, increased aortic blood flow appears to inhibit AAA expansion [154]. Magnetic resonance imaging in patients with AAA who have exercised has demonstrated increased abdominal aortic blood flow [155], and thus, exercise may have the potential to limit AAA expansion in humans as well. Although the exact mechanisms remain to be determined, exercise reduces the levels of systemic markers of inflammation relevant to AAAs. One trial that randomly assigned 140 patients with AAA <5.5 cm found no significant effect of an exercise program on AAA expansion rates over an average of 23 months [156,157]. There were marked improvements in exercise capacity in the training group, and there was a modest inverse association between the change in exercise capacity and change in AAA diameter. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "The benefits and risks of aerobic exercise".)

Uncertain benefit for limiting AAA expansion — A number of drug targets that may inhibit AAA formation or progression have been identified in animal models and in vitro studies. These studies have generated much interest for the treatment of patients with small aneurysms; however, to date, there is no proven evidence that any of these targets unequivocally prevents aortic expansion and rupture [158-164]. A multicenter study that identified 5362 patients with AAA found no significant association between AAA progression and usage of statins, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers [165].

Beta blocker therapy — Beta blockers have a role in managing patients with cardiovascular disease, but they have not been clearly shown to reduce aneurysm expansion rates [166]. (See "Management of cardiac risk for noncardiac surgery", section on 'Beta blockers'.)

A number of early animal studies and retrospective reviews suggested that beta blockers may inhibit AAA expansion [166-170]. One study evaluated 121 patients with an infrarenal aortic aneurysm who were monitored by serial ultrasound examination; 38 of the patients were treated with a beta blocker [167]. The mean expansion rate was significantly lower in the patients receiving a beta blocker (0.36 versus 0.68 cm per year). However, two large trials found no significant differences in AAA expansion rates in patients receiving beta blockers compared with those who did not [166,171]. The lack of benefit may have been related to poor compliance due to the side effects of beta blockade that measurably diminished quality of life. Although these studies did not show a benefit for propranolol in limiting AAA expansion, they do not exclude the possibility that a better-tolerated selective beta-adrenergic blocker could be beneficial.

ARBs and ACE inhibitors — Although animal studies have suggested the utility of angiotensin receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in decreasing the rate of aneurysm expansion [172,173], the clinical use of these agents has not clearly demonstrated the same benefits [174]. Infusion of angiotensin II into rodents promotes AAA formation, which is thought to be due to aortic inflammation and proteolysis and not due to the secondary increase in blood pressure [175-177]. Angiotensin type 1 receptor blockade (ARB) usually [178-183], but not always [179], inhibits aneurysm development in various animal models such as AAAs induced by angiotensin II, AAAs induced by chemical agents, and AAAs in mice genetically predisposed to aneurysm. ACE inhibitors are not reliable for inhibiting experimental AAA development [178,179,184].

A number of clinical studies have associated reduced rates of AAA expansion or rupture with the use of ACE inhibitors and ARBs [174,185-187]. A study of 15,326 patients who presented with AAA (intact or ruptured) evaluated the prehospital use of ACE inhibitors [185]. Patients taking ACE inhibitors were significantly less likely to present with ruptured aneurysm compared with those who were not on ACE inhibitors (OR 0.82, 95% CI 0.74-0.90). By contrast, a report from the United Kingdom Small AAA study found an increased risk of AAA expansion for patients on ACE inhibitors [187]. A later multicenter trial randomly assigned 224 patients ≥55 years of age with AAA diameter 3.0 to 5.4 cm to perindopril arginine 10 mg, amlodipine 5 mg, or placebo [188]. Annual expansion rates (1.68, 1.77, and 1.81 mm, respectively) were similar between the groups, and similar numbers of patients in each group underwent elective surgery for AAA >5.5 cm diameter. In the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial, changes in CT-measured AAA diameters and the rate of AAA related events were also similar for telmisartan compared with placebo [189].

Other antihypertensive agents — Diuretics and calcium channel blockers have also been studied for their effects on AAA expansion. Although a trend toward lower expansion rates has been observed for calcium channel blockers, significant differences have not been seen [70]. Diuretics appear to have no impact on expansion rates.

Statin therapy — The pathogenesis of AAA involves diminished integrity of the arterial wall driven by local inflammation, an altered balance in arterial wall repair, and degradation by enzymes such as matrix metalloproteinases (MMPs) [190]. Statins reduce the expression of MMPs in a concentration-dependent manner, independent of their cholesterol-lowering effects [191,192].

Animal studies suggest that statins may limit AAA expansion [193-198]. However, the influence of statins for inhibiting atherosclerosis may be relatively greater [197]. No randomized trials have specifically assessed the effect of statins on AAA expansion or rupture. A number of observational studies have examined the effect of statin therapy on the expansion of small AAAs [128,139,186,187,199-204]. Early studies reported reduced rates of AAA expansion in patients treated with statins [128,139,200,202-204]; however, most larger studies have not confirmed a relationship [186,187,201,205,206]. In the Trømso study, statin therapy was associated with an increased risk of developing AAA (OR 3.8, 95% CI 1.45-9.81) [143]. However, in a population-based case control study that included 7168 patients, a decreased risk for AAA rupture was found for current statin users compared with never users (OR 0.70, 95% CI 0.61-0.95), a risk difference that persisted after adjustment for confounding factors [199]. However, multiple meta-analyses found no evidence that statins impact AAA expansion rate but did observe a survival benefit for those on statins [122,207]. Thus, although there is insufficient evidence to recommend the initiation of statin therapy solely for the treatment of AAAs [141], statin therapy should be considered for patients with AAA to reduce overall cardiovascular risk.

Metformin — Diabetes is associated with reduced expansion rates. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Negative risk factors'.)

Some have speculated that diabetes medication effects may play a role, either indirectly (ie, as a measure of increasing diabetes severity) and/or directly. Observational studies suggest reduced rates of AAA expansion in patients with diabetes who have a subscription for metformin [208-211]. Prospective randomized trials testing the efficacy of metformin in limiting AAA progression in patients without diabetes are either planned or underway in several different countries around the world.

Antiplatelet therapy — Antiplatelet therapy may influence the formation of thrombus within AAA and reduce progression in patients with small AAA, but a definitive association between platelet inhibition and aneurysm progression has not been identified [186].

The use of antiplatelet agents (eg, aspirin) is postulated to decrease thrombus formation, reduce aortic wall inflammation, and stabilize the aortic wall [212]. The volume of thrombus within AAAs correlates to maximum AAA diameter [213], and circulating concentrations of thrombin degradation products (D-dimer) are strongly associated with the presence of AAA and progression in patients with small AAAs [214,215]. Thrombus from human infrarenal AAAs also contains inflammatory cells [216,217]. In animal models, platelet inhibition has been found to limit AAA formation [217,218]. Although a number of clinical studies have been performed, antiplatelet therapy has not been evaluated in randomized trials [128,139,186,187,200-204,212]. In one study, ASA was associated with decreased rates of progression of small AAA [212]. However, larger studies have found no significant association between antiplatelet therapy and AAA expansion [186,187,201].

Anti-inflammatory agents — A characteristic histological feature of human AAA is a dense inflammatory infiltrate with a variety of cells, including macrophages, neutrophils, and lymphocytes, typically present [219,220].

Elastases (proteases) secreted from these cells degrade the normal arterial wall architecture and, particularly, the elastic lamellae. Aortic thrombus also contains neutrophils and high concentrations of proinflammatory cytokines and proteolytic enzymes [216,217]. Inhibition of these inflammatory cells suppresses the development of AAA in rodent models [221]. A number of protease inhibitors have been developed as antineoplastic agents, but most have side effects that would limit their use in patients with AAA [222].

Mast cells, which contain chymase and other proinflammatory cytokines, may contribute to AAA formation [223]. Mice that are deficient in this cell type are protected from experimental AAA [224,225]. These findings have raised interest in the use of mast cell stabilizing agents in patients with small AAAs. However, a trial that randomized 326 patients to pemirolast or placebo found no significant differences in small AAA (3.0 to 4.9 cm) expansion rates (mean 2.42 mm) over a 12-month period [226].

No benefit

Doxycycline — Randomized trials show that there is no benefit for doxycycline in reducing AAA expansion in spite of encouraging preclinical studies and may indicate that some of the available methods used for generating aneurysms in animals may be inadequate for modeling human disease.

It was initially postulated that aneurysm progression may be enhanced by secondary microbial infection within the aortic wall. Serologic evidence of Chlamydia pneumoniae infection was associated with an increased rate of AAA expansion [227], and two small trials suggested that roxithromycin may decrease AAA expansion rates [228,229]. Although infection is known to potentially lead to the formation of aneurysms, clear evidence supporting a role for infection in the formation and progression of the majority of AAAs (noninfected) has not been established [151,228]. It was recognized that the commonly used tetracycline antibiotics suppressed inflammatory markers [230,231], and inhibited matrix metalloproteinases (MMPs) in vitro [232] and in aneurysm tissue [233,234]. MMPs are postulated to play a role in aneurysm formation. In at least 14 separate studies in animal models, doxycycline has been found to inhibit aneurysm development and progression [161,235]. In two animal studies, rapamycin similarly inhibited experimentally induced AAA [236,237].

In humans, doxycycline does not reduce AAA expansion:

●The PHarmaceutical Aneurysm Stabilization Trial (PHAST) did not find a reduction in growth of small AAA (3.5 to 5.0 cm) following 18 months of doxycycline (100 mg daily) compared with placebo; rather, aneurysm expansion was greater in the doxycycline group (4.1 mm versus 3.3 mm), but this was not considered to be clinically relevant [238]. Doxycycline treatment did not influence the need for or timing of elective AAA repair. The study was limited by the high number of patients lost from the study due to nonadherence, adverse treatment effects, or elective AAA repair.

●A second trial with more complete follow-up randomly assigned 261 individuals 50 years or older with small infrarenal AAA (aortic diameter 3.5 to 5.0 cm for men, 3.5 to 4.5 cm for females) to 100 mg oral doxycycline or placebo twice daily [158,239]. Doxycycline did not reduce aneurysm expansion; the change in AAA maximum transverse diameter measured from CT images at baseline and follow-up at two years was similar (0.36 cm for each group). Mortality and the need for AAA repair were also similar. Loss to follow-up was low (3 percent) in this trial.

AAA REPAIR — Elective abdominal aortic aneurysm (AAA) repair is the most effective management to prevent rupture. Two methods of aneurysm repair are currently available: open surgery and endovascular aneurysm repair (EVAR). The mortality of elective AAA repair is 3 to 5 percent for open AAA repair but lower at 0.5 to 2 percent for EVAR [240-242]. When choosing the type of repair, it is important to take into account the patient's expected survival (short-term and long-term), which depends upon the patient's age and medical comorbidities. (See 'Medical risk assessment' above.)

●Open AAA repair – Open aneurysm repair involves replacement of the diseased aortic segment with a tube or bifurcated prosthetic graft (figure 5) through a midline abdominal or retroperitoneal incision [243]. With technical refinements for open AAA repair, complications such as acute renal failure, distal embolization, wound infection, colonic ischemia, false aneurysm formation, aorto-duodenal fistula, graft infection, and perioperative bleeding have become less common following routine elective surgery but remain significant issues following emergent open AAA repair.

●EVAR – EVAR involves the placement of modular graft components delivered via the iliac or femoral arteries to line the aorta (figure 5) and exclude the aneurysm sac from the circulation. EVAR requires fulfillment of specific anatomic criteria. Up to 70 percent of patients are EVAR candidates. This percentage is expected to increase with the approval of specialized endograft designs that will allow the treatment of more challenging aortic aneurysm anatomy. Although EVAR is associated with lower perioperative mortality, late AAA rupture has been reported.

Summary of indications for elective AAA repair — Repair of asymptomatic AAA is generally indicated under the circumstances listed below. These indications are discussed in more detail above. Repair of symptomatic (nonruptured) and ruptured AAA are discussed separately. (See 'Aneurysm repair versus conservative management' above and "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm".)

●Asymptomatic AAA ≥5.5 cm in males; asymptomatic AAA > 5.0 in females

●Rapidly expanding AAA

●AAA associated with peripheral arterial aneurysm (eg, iliac, popliteal) or symptomatic peripheral artery disease (eg, iliac occlusive disease) undergoing revascularization

Outpatient versus inpatient preoperative evaluation — Most patients with asymptomatic AAA can be managed on an outpatient basis. For those with indications for AAA repair, the patient and their family or other caretakers should be counseled regarding the risk of rupture prior to definitive repair and informed of potential symptoms that can be associated with AAA and encouraged to communicate the development of any symptoms to their surgeon and primary care physician. (See "Open surgical repair of abdominal aortic aneurysm", section on 'Preoperative evaluation' and "Endovascular repair of abdominal aortic aneurysm", section on 'Anatomic suitability'.)

On occasion, a patient will present clinically with a very large (≥6.0 cm in diameter) asymptomatic AAA that may warrant admission and inpatient evaluation. Although there are no data to assist with clinical management of very large, asymptomatic AAA or any uniformly accepted standards of care, we suggest immediate referral to a vascular surgeon because of the high risk for rupture. We suggest earlier rather than later aneurysm repair once appropriate preoperative studies, medical risk assessment, and assessment of aortoiliac anatomy are completed. There is no advantage to an excessive delay. For patients found to have a very large, asymptomatic AAA in a practice setting that does not have vascular expertise, we suggest referral to a vascular center in a timely manner.

Very large, asymptomatic AAA has an estimated rupture risk over a 12-month period of 10 to 20 percent for those between 6 and 7 cm, 20 to 40 percent for those 7 to 8 cm, and 30 to 50 percent for those larger than 8 cm. The rupture risk over a period of weeks or months during the intervening period from the time of initial diagnosis and definitive treatment is not known. Rupture can occur during this interval. Because of the potential for rupture, some vascular surgeons routinely admit patients with very large, asymptomatic AAA for preoperative evaluation, but the validity of this practice has not been substantiated.

Open versus endovascular aneurysm repair — Randomized trials comparing open AAA repair with EVAR have found significantly improved short-term (30-day) morbidity and mortality for EVAR but no significant differences in long-term outcomes up to 10 years [77,244-253]. A pooled analysis of these trials identified a 69 percent reduction in the risk for perioperative mortality for endovascular compared with open repair (odds ratio [OR] 0.33, 95% CI 0.17-0.64) [254]. EVAR appears to be associated with the need for more secondary procedures and an ongoing future risk of aortic rupture. However, there appears to be no significant differences in overall complication rates when all complications for each procedure are included [255]. The important points of these randomized trials are summarized below.

DREAM trial — The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial randomly assigned 351 patients to open repair or EVAR [76]. All patients had AAA >5 cm in maximal diameter and were suitable candidates for either technique.

The perioperative (30-day) mortality rate was lower for EVAR compared with open AAA repair (1.2 versus 4.6 percent), though this result was not significant. At two-years post-randomization, the cumulative rates of aneurysm-related death remained less for EVAR (2.1 versus 5.7 percent) compared with open repair, a difference that was entirely due to the initial perioperative outcomes [247]. However, there were no significant differences in overall survival (89.7 percent for EVAR and 89.6 percent for open repair). The perioperative survival advantage seen with EVAR was not sustained after the first postoperative year, due to an increase in non-aneurysm-related mortality in the EVAR group. These results were maintained at six years with survival rates for EVAR at 68.9 percent and open repair at 69.9 percent [248].

The rate of moderate and severe systemic complications was significantly lower for EVAR (11.7 versus 26.4 percent) compared with open repair. Rates of moderate and severe vascular or graft-related complications were significantly greater for EVAR (16.4 versus 8.6 percent) compared with open repair. The need for secondary vascular intervention was significantly higher for EVAR (29.6 versus 18.1 percent) compared with open repair.

EVAR-1 trial — The endovascular aneurysm repair versus open repair in patients with AAA (EVAR1) trial randomly assigned 1252 patients to AAA repair with EVAR (n = 626) or open AAA repair (n = 626) [249]. Perioperative (30-day) mortality was significantly less for EVAR (1.8 versus 4.3 percent). No significant differences were seen in overall mortality, and graft-related complications occurred more frequently with EVAR. New complications related to EVAR continued to occur out to eight years of follow-up [77]. The early benefit of EVAR was lost beginning approximately eight years after randomization due to late fatal secondary aneurysm ruptures. Over a mean of 12.7 years of follow-up, the overall mortality rate was similar (9.3 versus 8.9 deaths per 100 person-years for the EVAR and open groups, respectively) [256]. However, aneurysm-related mortality was significantly increased for EVAR after eight years (7 versus 1 percent) and was mainly attributable to secondary aneurysm sac rupture. Whether newer-generation stent-grafts would have these same long-term aneurysm-related risks is unknown; over one-third of the stent-graft devices received by the enrollees in this study are no longer used [249].

Another finding of longer-term follow-up was that the number of cancer deaths was 50 of 179 in the EVAR group and 31 of 154 in the open group (after eight years, adjusted hazard ratio 1.87, 95% CI 1.19-2.96). No other study has observed an increased cancer risk with the use of aortic stent-grafts. In the EVAR group, 37 of 50 of these cancer deaths were described as "other" (ie, not lung cancer). If these were abdominal cancers, their increased detection could be related to more frequent surveillance. Based upon estimated cancer risks [257,258], it is unlikely these can be attributed to imaging-related radiation exposure. Reintervention rates were significantly higher for EVAR compared with open repair.

A criticism of this trial was that all complications related to open repair, such as incisional hernia, were not included in the study. The short-term benefit of EVAR was lost due to late fatal aneurysm ruptures. The authors concluded that treatment by EVAR significantly reduced the operative mortality compared with open repair, but there were no long-term advantages of one type of repair for aneurysm-related or overall mortality.

OVER trial — The Open Versus Endovascular Repair (OVER) trial is an ongoing multicenter trial at the Veterans Affairs Medical Centers that randomly assigned 881 veterans ≥49 with AAA >5.0 cm, an associated iliac aneurysm with maximal diameter ≥3.0 cm, or a diameter of ≥4.5 cm with rapid enlargement (defined as 0.5 cm growth in six months or 1.0 cm in one year) to open AAA repair or EVAR [78,251,259]. Patients were candidates for either type of repair.

EVAR was associated with significantly shorter procedure times (2.9 versus 3.7 hours), a shorter duration of mechanical ventilation (3.6 versus 5.0 hours), shorter intensive care unit stay (1 versus 4 days), shorter length of hospital length (3 versus 7 days), and lower transfusion requirements (0 versus 1 unit).

Overall mortality was not significantly different between the groups (68 percent EVAR, 70 percent open repair) over 14 years of follow-up [251,259]. There was a postoperative survival advantage for endovascular repair (0.5 versus 2.5 percent; between group difference -2.1 percent, 95% CI -3.7 to -0.5), and overall survival initially appeared higher in the endovascular group up to four years follow-up, but thereafter, no significant differences were seen. There was also no significant difference in aneurysm-related death (overall 28/608; 12 endovascular; 16 open repair).

Aneurysm rupture (confirmed) occurred in more patients in the endovascular group (7 versus 1; between group difference 1.3 percent, 95% CI 0.1-2.6). The aneurysm rupture in the open repair patient occurred in the thoracic aorta. There were no significant differences for other causes of death. It is important to note that the cause of death was not known or could not be verified for 93 patients (8.6 percent of endovascular; 12.6 percent of open repair).

In addition, significantly more patients in the endovascular-repair group underwent secondary procedures (27 versus 20 percent; between group difference 6.9 percent, 95% CI 2.0-17.5). In this trial, incisional hernia was included as an open-repair-related secondary procedure. A separate database review found similar complication rates between open and endovascular repair when all complications were included [255].

ACE trial — The Aneurysme de l'aorte abdominale: Chirurgie versus Endoprothese (ACE) trial randomly assigned 316 patients with AAA >5 cm to EVAR or open surgery [250]. As with the studies above, there were no significant differences in the cumulative survival or major adverse events rates (95.9 versus 93.2 percent at one-year follow-up, and 85.1 versus 82.4 percent, respectively, at three-year follow-up). In-hospital mortality was also not significantly different (0.6 versus 1.3 percent). The need for reintervention was higher in the EVAR group (16 versus 2.4 percent), compared with open AAA repair, although incisional hernia repair was not considered.

Choice of AAA repair approach — When it has been determined that a patient should undergo elective AAA repair, we agree with guidelines from major medical and surgical societies that emphasize an individualized approach when choosing the type of AAA repair, taking into account the anatomic factors, patient age, sex, risk for AAA rupture, and risk for perioperative morbidity and mortality [4,7,9,260-267]:

●Endovascular repair may be preferred in patients with favorable anatomy (as defined by the "instructions for use" of a given device) who are at a high level of perioperative risk.

●Endovascular repair may be appropriate in patients with favorable anatomy but who do not have a high surgical risk.

●Open surgical repair may be preferred for younger patients who have a low or average perioperative risk.

Based upon the randomized trials presented above, the main benefits of EVAR appear to be the greatest in the short term, and thus, EVAR is the most appropriate choice for patients with a limited life expectancy and those with a high level of perioperative risk. In a review of studies limited to patients 80 years of age or older, perioperative mortality, overall complications, and specific complications (cardiac, renal, pulmonary, bleeding) were all significantly reduced for endovascular compared with open surgical repair [268]. At three- and five-year follow-up, survival was similar in the two groups.

However, whether younger patients who are not at high risk for open surgery should undergo open surgical repair versus EVAR remains controversial [269-273]. Surveillance of endovascular stent grafts over an extended period of time exposes the patient to greater levels of cumulative radiation; however, ultrasound surveillance is becoming more common. Although EVAR does not eliminate the risk of future aortic rupture, this is also true for open AAA repair, which can have late complications such as anastomotic pseudoaneurysm (proximal, distal) and development/progression of iliac or suprarenal aneurysms. In a Veterans administration study in the United States that assessed total mean costs related to open versus endovascular repair, there were no significant differences (mean 5.2 years follow-up) [274]. (See "Endovascular repair of abdominal aortic aneurysm", section on 'Endograft surveillance' and "Complications of endovascular abdominal aortic repair".)

In the United States, about 80 percent of AAAs are repaired using an endovascular approach [275]. For patients with anatomy that is suitable for endovascular repair (ie, as defined by the instructions for use of a given device), the authors speculate that this rate is nearly 100 percent, given that most of the limitations to EVAR have fallen away with newer generation devices, as well as a better understanding of the modes of failure following endovascular repair. However, the management of AAA varies widely worldwide, with percentages of EVAR that can be much lower, largely related to variations in availability of equipment, levels of training, and reimbursement policies [275].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Aortic and other peripheral aneurysms" and "Society guideline links: Acute extremity ischemia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Abdominal aortic aneurysm (The Basics)")

●Beyond the Basics topics (see "Patient education: Abdominal aortic aneurysm (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Abdominal aortic aneurysm – Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Approximately 7000 deaths per year are attributed to ruptured AAA in the United States. Without repair, ruptured AAA is nearly uniformly fatal. For asymptomatic patients, elective repair of the aneurysm is the most effective management to prevent rupture. (See 'Introduction' above.)

●Asymptomatic small AAA – For most patients with asymptomatic infrarenal AAA <5.5 cm, we recommend conservative management (watchful waiting) rather than elective AAA repair (Grade 1A). The risk of aneurysm rupture does not exceed the risk of repair until the aneurysm diameter reaches 5.5 cm. However, there are situations for which elective repair of asymptomatic AAA <5.5 cm may also be appropriate. These may include rapidly expanding AAA (>0.5 cm in six months or >1 cm per year), coexistent aneurysm/peripheral artery disease, and female sex. (see 'Aneurysm repair versus conservative management' above):

●Conservative management – Conservative management consists of periodic clinical evaluation and imaging surveillance to identify AAA that exceeds the threshold for repair or is rapidly expanding. Medical therapies for patients with AAA focus on the management of modifiable risk factors for AAA and cardiovascular disease with the goals of reducing the need for intervention due to aneurysm expansion or rupture, reducing morbidity and mortality associated with AAA repair, and reducing cardiovascular morbidity and mortality. (See 'Conservative management' above.)

•Smoking cessation – For patients with AAA who smoke, we recommend smoking cessation (Grade 1A). Smoking is strongly associated with AAA expansion and rupture and is the most important modifiable risk factor. Even though reduced aneurysm expansion and rupture risk have not been clearly demonstrated among those who have stopped smoking, smoking cessation has other clear benefits. (See "Benefits and consequences of smoking cessation".)

•No medical therapies proven to limit AAA expansion – Although many pharmacologic therapies aimed at limiting AAA expansion and preventing rupture have been tried, no therapy has been proven successful at achieving these goals, and as such, we suggest not implementing any of the pharmacologic therapies discussed above for the sole purpose of treating AAA (Grade 2C). (See 'Therapies to limit aortic expansion' above.)

●Asymptomatic large AAA – For good-risk surgical candidates (open or endovascular repair) with AAA >5.5 cm, we recommend elective AAA repair (Grade 1A). For patients with AAA >5.5 cm who have a short life expectancy (<2 years) due to advanced comorbidities, particularly cardiopulmonary disease or malignancy, we suggest no repair over endovascular aneurysm repair (Grade 2B). For these patients and others who elect not to undergo repair, ongoing AAA surveillance is not needed. The patient should be encouraged to create an advanced directive detailing their wishes for no repair of any kind in the event of rupture. Family members or other caretakers should be made aware of these wishes, given that the patient may not be able to report their wishes at the time of aneurysm rupture. (See 'Summary of indications for elective AAA repair' above and 'Counseling the high-risk patient' above.)

●AAA repair – The primary goals of aneurysm repair are to prevent rupture while minimizing morbidity and mortality associated with repair. We agree with guidelines from major medical and surgical societies that emphasize an individualized approach when choosing between an open or endovascular approach to AAA repair, accounting for aortic anatomy, patient age, life expectancy, and risk factors for perioperative morbidity and mortality. For patients with favorable anatomy for endovascular repair (as defined by the instructions for use of a given device) and a high level of perioperative risk, we recommend endovascular repair, rather than open surgical repair (Grade 1B). (See 'Open versus endovascular aneurysm repair' above.)

●Surveillance schedule for unrepaired AAA – The optimal surveillance schedule for patients who are not undergoing AAA repair is not known for certain. The Society for Vascular Surgery (SVS) recommends surveillance every 6 to 12 months using ultrasound or CT for medium-sized aneurysms (4 to 5.4 cm in diameter) but less frequent intervals for smaller aneurysms. We frequently perform surveillance on small aneurysms annually to minimize imaging variability and alleviate patient anxieties. Annual clinical examination and risk reduction assessment can also be performed concurrently with AAA surveillance. (See 'Follow-up and surveillance' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review.